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Increased expression of phospho-acetyl-CoA carboxylase protein is an independent prognostic factor for human gastric cancer without lymph node metastasis

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Abstract

Upregulation of acetyl-CoA carboxylase (ACC), as a rate-limiting enzyme of fatty acid synthesis,has been recognized in multiple human cancers, implicating a critical role in cancer development and progression; yet, its role in gastric cancer still remains unclear. In the present study, we detected ACC and phosphorylated form of ACC (pACC) expression in gastric cancers and explored its clinical significance. Tissue microarray blocks containing primary gastric cancer and adjacent normal mucosa specimens obtained from 1,072 Chinese patients were used for the detection of ACC and pACC expression by immunohistochemistry. Gastric cancer cell lines were treated by metformin, and pACC was measured by Western blotting. ACC overexpression was observed in all the tumor specimens. High expression of pACC was found in 630 (58.8 %) of the 1,072 primary tumors and in 237 (66.6 %) of the 356 primary tumors without lymph node metastasis. Absent/low expression of pACC significantly correlated with advanced T stage (P < 0.001), tumor size (P = 0.010), lymph node metastasis (P < 0.001), advanced disease stage (P < 0.001), and poor histological differentiation (P = 0.014) in 1,072 primary tumors, and with advanced T stage (P = 0.015), tumor size (P = 0.017), and poor histological differentiation (P = 0.001) in 356 tumors without lymph node metastasis. Kaplan–Meier analysis showed that high expression of pACC is strongly related to better survival rates in all gastric cancer patients (P = 0.006). Cox regression analysis revealed that pACC is an independent prognostic factor only in patients without lymph node metastasis (P = 0.016). Metformin treatment leaded to increased expression of pACC, which, in turn, resulted in the reduction of cell proliferation and colony formation of gastric cancer cells (P < 0.05). Increased activation of ACC is frequent in human gastric cancer, and downregulation of pACC is an important prognostic factor, suggesting that ACC/pACC might be a potential target for cancer intervention.

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Acknowledgments

This work was partly sponsored by Natural Science Foundation of China (30901794) and Shanghai Pujiang Program (13PJD002).

Conflict of interest

We declare no conflicts of interest with any other person or units.

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Authors and Affiliations

  1. Department of Medical Oncology, Changzheng Hospital, Hetian Road 64, Shanghai, 200070, People’s Republic of China

    Wenzhang Fang, Jiejun Wang & Guanzhen Yu

  2. Department of Oncology, Fuzhou General Hospital, Fuzhou, Fujian Province, People’s Republic of China

    Wenzhang Fang

  3. Department of No. 3 Cadre Wards, General Hospital of Jinan Military Area Command, Jinan, Shandong Province, People’s Republic of China

    Hongmei Cui

  4. Department of Ophthalmology, Kunming General Hospital of Chengdu Military Command, Kunming, Yunnan Province, People’s Republic of China

    Danyang Yu

  5. Department of Pathology, Changhai Hospital, Shanghai, People’s Republic of China

    Ying Chen

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  1. Wenzhang Fang
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  4. Ying Chen
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Correspondence to Guanzhen Yu.

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Wenzhang Fang, Hongmei Cui, and Danyang Yu have contributed equally to this work.

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12032_2014_15_MOESM1_ESM.pptx

Kaplan–Meier plot of overall survival durations in the patients with different TNM stages according to pACC expression. (A) Graphical representation of the differences of pACC staining between stage I/II and stage III/IV. (B) Survival durations were significantly worse in patients of stage I/II disease with low expression of pACC (median survival, 81.7mo) than in those with high expression of pACC (median survival, 92.2mo; P = 0.016). (C) No statistical significance of the survival durations was observed between patients of stage III/IV disease with high expression of pACC and those with low expression of pACC (PPTX 104 kb)

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Fang, W., Cui, H., Yu, D. et al. Increased expression of phospho-acetyl-CoA carboxylase protein is an independent prognostic factor for human gastric cancer without lymph node metastasis. Med Oncol 31, 15 (2014). https://doi.org/10.1007/s12032-014-0015-7

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  • DOI: https://doi.org/10.1007/s12032-014-0015-7

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